The purpose of the proposed research is to investigate protein-DNA interactions in human chromosomes in cells from healthy and diseased individuals. The structural organization, replication, stability and repair of human chromosomes will be studied by spectroscopic, biochemical, and cell biological techniques. Methods will be developed and utilized in attempts to understand genetic control, in particular X chromosome inactivation, and inherited conditions with increased susceptibility to neoplastic transformation. BIBLIOGRAPHIC REFERENCES: Latt, S.A. and Stetten, G.: Spectral Studies on 33258 Hoechst and Related Bisbenzimidazole Dyes Useful for Fluorescent Detection of Deoxyribonucleic Acid Synthesis. J. Histochem. Cytochem. 24:24, 1976. Zack, G.W., Spriet, J.A., Latt, S.A., Granlund, G.H. and Young, I.T.: Automatic Detection and Localization of Sister Chromatid Exchanges. J. Histochem. Cytochem. 24:168, 1976.